tbuckley/cabot-search huggingface dataset:
PB2189: HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH SEVERE CONGENITAL NEUTROPENIA:A CASE REPORT OF 13 YEARS OLD PATIENT
Authors: J. Wang, K. Liu, S. Cui, X. Dong, W. Zheng, Z. Liu, R. Xu, Y. Wang, J. Xu, F. Kong
Journal: HemaSphere (2022)

Background: Haploidentical hematopoietic stem cell transplantation in patients with severe congenital neutropenia:A case report of 13 Years old patient Aims: Severe congenital neutropenia (SCN) is a heterogeneous group of diseases progressing with arrest of maturation in bone marrow. It is characterized by recurring skin, lung, and deep tissue infections from the first months of life. The use of G-CSF therapy has radically changed these patients’ outlook. However, a minority of patients is refractory to G-CSF, and some undergo malignant transformation. Methods: Allogeneic hematopoietic stem cell transplantation (HSCT) appears to be the only curative treatment for such patients. We report a 13 years femal patient who presented in years of life with severe neutropenia with a mutation in ELANE. This patient is allergic to a variety of antimicrobial drugs, difficult to treat, low quality of life, and has a high possibility of conversion to leukemia. In order to improve the quality of life, reduce the risk of conversion to leukemia and prolong its survival time, the transplantation treatment procedure was started through communication with patients and their families.Since the patient has no sibling full donor, the donor chooses the non consanguineous half matched donor sought by the bone marrow bank. The patient received conditioning regimens used for leukemia (myeloablative regimens),including CY (120–200 mg/kg) and BU (16–20 mg/kg or 560 mg/m2 administered orally, generally divided into 16 doses). In addition to the BU and CY combination, the agents used for conditioning included ATG. Results: The transplantation process was smooth, with granulocyte implantation on day + 14 and platelet implantation on day + 22. The hemogram returned to normal after 48 days. The STR-PCR was detected on + 30d, + 60d, + 90d, + 180d and + 270d respectively to evaluate the evidence of implantation and the chimeric body showed complete chimerism after transplantation. So far, the patient has survived without events for 20 months. After transplantation, the patient’s congenital gene ELANE mutation disappeared. Summary/Conclusion: Adolescents with SCN who long term dependence on G-CSF can receive haploidentical allogeneic hematopoietic stem cell transplantation.
PB2241: CHARACTERISTICS AND OUTCOME OF WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA) IN ADULTS: A RETROSPECTIVE ANALYSIS OF 110 TUNISIAN PATIENTS
Authors: E. Bouslama, A. Dhib, K. Zahra, H. Regaieg, N. Bensayed, W. bouteraa, M. Zaier, Y. ben youssef, A. khelif
Journal: HemaSphere (2022)

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease caused by increased erythrocyte destruction by immunoglobulin G (IgG) autoantibodies, with or without complement activation. Aims: To study the clinical characteristics, outcomes, and survival of warm-type autoimmune hemolytic anemia (wAIHA) patients (pts). Methods: This study was a retrospective study from 2001 to 2020. Clinical data of wAIHA pts from a single referral center in Tunisia were reviewed and analyzed. Results: One hundred and ten pts (59.1% females) were included. The mean age at the time of wAIHA onset was 54 (range 19 to 98). All the pts had a positive DAT. Results of DAT showed IgG in 77 pts (70%) and IgG plus C3d in 33 pts (30%). Primary wAIHA was found in 58 pts (52.7%). Fifty-two (47.3%) of wAIHA cases were secondary: lymphoproliferative diseases (30 patients), connective tissue disease (14 patients: 5 systemic lupus, 3 vitiligo, 2 rheumatoid arthritis, 1 anti-phospholipid syndrome, 1 ankylosing spondylitis, 1 Hashimoto’s thyroiditis, 1 Basedow’s Disease), Evan’s syndrome (5 patients), cancer (3 pts). Corticosteroids were the first line therapy with an overall initial response rate of 73%. Thirty-six (32,7%) of the pts were corticosteroid-dependant and 20 pts (18.1%) required at least one second-line treatment including Rituximab (3), splenectomy (5) and Cyclophosphamide (12). After a mean follow-up of 44 months, 53 pts (48.2%) were in remission and off treatment. Twenty-seven (24.5%) had died. Infection was the most common cause of death (11 pts). Other causes of death were: 1 ischemic stroke and 5 progression of hematologic malignancies or cancer. Secondary wAIHA were associated with reduced response to corticosteroids and increased need for second-line therapy. Summary/Conclusion: This study confirms gender distribution in wAIHA and shows a high proportion of secondary wAIHA. Most patients have responded initially to steroids. The mortality rate was high, with sepsis as a leading cause of death.
Abstract 6283: Reannotation and normalisation of Infinium 850k data for improved analysis of methylation at enhancers and non-coding RNAs
Authors: Martin Bizet, Matthieu Defrance, Emilie Calonne, Gianluca Bontempi, François Fuks, Jana Jeschke
Journal: Cancer Research (2022)

Abstract In this study, we evaluated the MethylationEPIC BeadChip (850k) technology for enhancer methylation analysis with respect to RRBS, both high-throughput technologies commonly used to screen large patient cohorts. We developed and applied a new approach to re-annotate the 850k data, which greatly improved the association of probes to enhancers and show that 850k targets more enhancers than RRBS. We further investigated the reproducibility of the two technologies and applied various existing normalization methods to 850k data that reduce variability between replicates and variability with other technologies. We thereby showed that normalization methods developed for 450k greatly reduced variability in 850k data to a level below that of highly variable RRBS data. We finally performed differential methylation analysis with 850k data from breast cancer samples applying our new re-annotation method and highlight that the majority of differentially methylated cytosines were detected with probes specific to the 850k mapping to enhancers, confirming the deregulation of enhancer methylation in breast cancer. In summary, our study provides a new annotation for the 850k array, which greatly increases the number of cytosines mapping to enhancers and therefore allows for the improved analysis of enhancer methylation. Overall, we conclude that the 850k array allows for detection of methylation changes in regions not covered by previous Infinium arrays and is the best choice, as compared to RRBS, for high-throughput analysis of enhancer methylation in large clinical cohorts. Citation Format: Martin Bizet, Matthieu Defrance, Emilie Calonne, Gianluca Bontempi, François Fuks, Jana Jeschke. Reannotation and normalisation of Infinium 850k data for improved analysis of methylation at enhancers and non-coding RNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6283.
P388: PREFERENTIAL SYNERGISTIC EFFECT OF INDISULAM IN COMBINATION WITH VENETOCLAX AND AZACYTIDINE IN AML CELLS WITH SF3B1 MUTATIONS.
Authors: P. Bernardo, M. Pereira, B. Galvão, J. Desterro, A. Nunes, M. D. J. Frade, J. Lobato, M. G. da Silva, M. Lemos, M. Silva, P. Ribeiro, S. Matos, N. Custódio, M. Carmo-Fonseca
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor prognosis characterized by a high rate of relapse after conventional combination chemotherapy, highlighting the need for improved therapeutic interventions. Genes involved in pre-mRNA splicing, namely SF3B1, U2AF1 and SRSF2, are frequently mutated in AML.Recent studies suggest that pharmacological targeting of the splicing machinery results in preferential lethality of splicing mutant AML cells, potentially providing a novel strategy for treatment of this disease. Existing anti- cancer sulfonamides have been shown to interfere with splicing and induce preferential killing of splicing mutant AML cell lines. A particular sulfonamide drug, indisulam, was previously studied in cancer clinical trials where it was found to be safe but demonstrated limited efficacy, most likely because neither the mechanism of action nor potential biomarkers of response were known. Aims: We investigated, in this study, the efficacy of indisulam, either alone or in combination with ABT-199 (venetoclax) and azacitidine, in cultured primary human AML cells. Methods: Bone marrow cells were collected from adults newly diagnosed with AML, non-treated. Cells were cultured and incubated for 48 and 72 hours with indisulam at a range of nanomolar concentrations. Additionally, cells were incubated with ABT-199 (10nM) and azacitidine (1μM), alone or in combination with indisulam. Cell viability and cell death were measured. For mutation profiling, a targeted myeloid gene panel was used. Results: We found that treatment with indisulam resulted in lethality of primary AML cells harboring mutations in SF3B1, but had minor or no effect on AML cells with other mutations including mutations in splicing factors U2AF1 and SRSF2. In SF3B1-mutated cells, a clear synergistic effect was further observed when indisulam was combined with ABT-199 and azacitidine. The correlation between efficacy of indisulam and synergy with ABT-199 and azacitidine in AML cells with different mutations will be shown and discussed. Summary/Conclusion: Our results indicate that indisulam is preferentially active and synergistic with venetoclax and azacitidine in SF3B1-mutated cells from newly diagnosed, non-treated AML patients.
P373: CIRCULATING ENDOTHELIAL PROGENITOR CELLS AND METABOLIC FACTORS IN CHILDHOOD CANCER SURVIVORS
Authors: E. Athanasopoulos, G. Martimianaki, P. Iordanis, M. Stratigaki, N. Katzilakis, E. Stiakaki
Journal: HemaSphere (2022)

Background: Circulating Endothelial Progenitor cells (cEPCs) participate in the regulation and maintenance of vascular integrity, balancing the coagulation–anticoagulation mechanisms, as well as the immune response. Obesity and hypertension constitute late effects of chemotherapy in children and numerous studies have shown a decrease in cEPCs number, underlining poor vascular repair capability. Aims: The determination of cEPCs in children treated for Acute Lymphoblastic Leukemia (ALL), Lymphomas (LYM) and solid tumors (ST) and the study of their levels in correlation with patients’ Body Mass Index (BMI) and blood pressure (BP) in different post-treatment time points. Methods: Peripheral blood from children with ALL (n=166), LYM (n=37), ST (n=109) and children without malignancies (Control, n=191) were studied. The cEPCs population was determined by Flow cytometry based on CD34, CD45, CD133, VEGFR2 expression. The BMI and the blood pressure (BP) values were registered and the corresponding percentiles calculated. Patients were divided into three groups: <1 year post-treatment, ≤1-3 years post-treatment, and ≥3 years after completion of treatment. Statistical analysis was performed using t-test (Holm-Sidak) and 2way ANOVA (Tukey’s multiple comparisons test). Results: In ALL group decreased levels of CD34+VEGFR2+ and CD34+CD133+VEGFR2+ were estimated in contrast with the LYM, ST and Control group (p=0,0144, 0,0262 respectively). Decreased levels of both populations were observed immediately after treatment completion in ALL, while in the post treatment period the levels gradually increased. On the contrary, in the LYM and ST group, at completion of treatment higher level of cEPCs were measured which gradually decreased (p= 0,0405 & 0,0026 respectively). The obesity was correlated with higher levels of cEPCs in the ST and LYM compared to the ALL group. The hypertensive patients had elevated cEPCs. Image:Summary/Conclusion: Conditions causing vascular damage such as obesity and hypertension are correlated with increased cEPCs in patients treated for ALL, LYM and ST. The effect of treatment seems to have a different impact in these groups, possibly not only related with the biology of the disease but with the differences of treatment protocols as well. The increase of cEPCs during the 1st post-treatment year probably reflects an effort to repair vascular damage caused by the treatment. Further investigation is needed to clarify these results.
Very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes pancreatic fibrosis
Authors: Xuguang Yang, Jie Chen, Jun Wang, Shuai Ma, Wenxue Feng, Zhihao Wu, Yangyang Guo, Hong Zhou, Wenli Mi, Wei Chen, Bo Yin, Yuli Lin
Journal: Immunity (2022)
PB2214: SCD POPULATION SURVEY IN ALBANIA, A PROSPECTIVE NON-INTERVENTIONAL MULTI-CENTER STUDY EVALUATING DISEASE AND PATIENTS CHARACTERISTICS OF SICKLE CELL DISEASE IN ALBANIAN SCD POPULATION
Authors: A. Cili, E. Petrela, A. Zaka, A. Hatellari, P. Pulluqi, T. Caja, A. Perolla, E. Calliku, M. Kreka, E. Dollaku, X. Ngjela, A. Memini, A. Kaleci, A. Ivanaj
Journal: HemaSphere (2022)

Background: SCD is a group of inherited disorders affecting hemoglobin (Hb) synthesis. Sickle cell erythrocytes have a mutant form of Hb, sickle Hb (HbS), which turns normally pliable erythrocytes into rigid, sickle-shaped cells. We conducted a survey project for generation of local data on SCD, to deeper understanding disease burden, patient journey treatment pathways and QoL and get insights on SCD epidemiology on national level, in our country Aims: The study answered the following main research question: What is the frequency (number per year) of vaso-occlusive crises (VOCs) and their overall QoL in patients with Sickle Cell Disease within routine treatment regimens in the real-world setting in Albania and different regions among permanent resident SCD patients? Methods: This study was a cross-sectional primary data collection NIS focused on disease that enrolled 242 patients with confirmed SCD diagnosis who signed patient consent forms. 10 selected physicians from Albanian Association of Hematology from 7 centers across the country fulfilled a questionnaire (survey) for each SCD patient, based on patient medical history (retrospective data) and interviewing the patient live (collecting primary data-EQ-5D instruments). Results: The study demonstrated in fatigue, 11% of patients reported “severe” and “very severe”; in pain/discomfort, 8% reported “severe” and “very severe”, while in mobility only 3.7% reported “severe” and “very severe”; in self-care, the majority of patients reported “no”, “mild” or “moderate” (respectively 86%, 11%, 2.5%); and usual activity dimensions, most of patients reported “no”, “mild”, “moderate” (respectively 64%, 26%, 7.4%). The data we received from our study corrected with the data from literature. Our study reported 37% of patients reported more than 2 VOCs requiring medical care (hospitalization or other medical facility visit and treatment with oral or parenteral narcotic agents or parenteral NSAIDs), while 67% of patients reported more than 2 VOCs in last 12 months managed at home. Image:Summary/Conclusion: This is the first study conducted in Albania in SCD disease area. The study demonstrated the local burden of SCD, the impact of the disease on QoL of SCD patients, one overall of prevalence, geographical distribution of SCD patients, clinical characteristics of sickle cell patients, treatment landscape and clinical practice in Albania. According to our results we concluded that in Albania the burden is considered moderate. The study concluded also some very important findings about the role of treatment and quality of life of SCD patients and the need for other treatment options to improve the outcomes of SCD patients.
PB2062: EPIDEMIOLOGICAL, CLINICAL AND THERAPEUTIC FEATURES OF REFRACTORY HODGKIN’S LYMPHOMA.
Authors: R. Ben Sghaier, Z. kmira, E. bouslama, M. zaier
Journal: HemaSphere (2022)

Background: Approximately 10 to 15 percent of patients have refractory Hodgkin’s lymphoma (HL) that either does not respond to initial therapy or progresses after an initial partial response. Refractory HL poses a major problem of care, especially since there is currently no consensus regarding second or third line chemotherapy. Aims: The objective of our study is to report the epidemiological, clinical and therapeutic features of patients with refractory HL to first-line chemotherapy. Methods: This is a retrospective study including 32 patients with refractory HL treated during the period from 2015 to 2020. The patients received the first line chemotherapy according to the national MDH 2015 protocol. Results: The median age of our patients was 33 years old (17-64years) with a sex ratio of 0.88. B symptoms at diagnosis were present in 53% of cases. Localized stage (II) and extented stages (III and IV) were observed in 25% and 75%, respectively. Tumor bulky (≥7cm) was present in 34.5% of cases. The International Prognostic Score (IPS) ≥3 was present in 31% of patients. Frontline treatment was ABVD chemotherapy in 4 patients with PR in 3 cases, progression in 1 case and BEACOPP-R chemotherapy in 28 patients with PR in 15 cases, failure in 8 cases and progression in 5 cases. First line salvage therapy was DHAP chemotherapy in 13 patients with CR in 2 patients, PR in 1 patient, failure in 3 patients, progression in 4 patients and toxic death in 3 patients. For patients refractory to DHAP (8patients), 7 patients received the second line salvage therapy which was IGEV in 2 patients with obtaining a PR in 1 patient and progression in the other patient and Bendamustin-Brentuximab (BB) in 5 patients with obtaining a CR in 3 patients and progression in 2 patients. First line salvage therapy was IGEV chemotherapy in 16 patients with CR in 4 patients, PR in 3 patients and progression in 9 patients. For patients refractory to IGEV (12patients), the second line therapy was DHAP with obtaining a CR in 2 patients, toxic death in 4 patients and failure in 4 patients who received (BB) as third line therapy without response. First line salvage therapy was BB chemotherapy in 3 patients with obtaining a CR in 1 patient and death during chemotherapy in 2 patients. For good responders after salvage therapy (11 /32 patients), autologous stem cell transplant (ASCT) was performed only in 3 patients. The 5 years overall survival and relapse free survival were 49% and 18%, respectively. Summary/Conclusion: Our results are much lower than the literature with a mediocre survival of these refractory forms encouraging the introduction of BB as protocol of salvage therapy and the respect of the ACSP in the good responders.
P1340: RESPONSE RATES AND PROGNOSTIC FACTORS IN ACUTE GASTROINTESTINAL GRAFT-VERSUS-HOST DISEASE
Authors: J. Freitas, M. Pimenta, E. Couto, P. Coelho, R. Branca, C. Pinho Vaz, L. Leite, A. Campos
Journal: HemaSphere (2022)

Background: Graft-versus-host disease (GVHD) continues to be the major lethal complication of allogeneic hematopoietic stem cell transplantation (HCT). The standard first-line therapy for acute GVHD is high-dose steroids, but 50% of cases are steroid refractory (SR), typically involving the gastrointestinal (GI) tract. Unfortunately, there is no established second-line therapy for GVHD which the response rates are typically low (20–40%) and the overall survival is poor, highlighting the urgent need for better therapies. Aims: Evaluate the response rates and prognostic factors of GI-GVHD patients Methods: GI-GVHD was diagnosed clinically and/or histologically and graded by MAGIC criteria. Patients whose GI-GVHD progressed within 3 days after the initiation of therapy or who failed to improve by at least one stage within 5 days were defined as non-responders. The overall response rate (ORR) to GVHD treatment was evaluated retrospectively at 4 weeks from the first day of first-line therapy. Survival outcomes were assessed by the Kaplan-Meier method. In the univariate analysis, OS were compared using the Log rank test. In multivariate analyses, the Cox proportional hazard regression model was performed for OS. A p<0.05 was considered to be statistically significant. Results: 351 patients (pts) were submitted to allogeneic HCT and 67pts (19.1%) had GI-GVHD at our institution between 2016 and 2021. The median time of onset of GI-GVHD was 37 days [7-92]. According to grading, 15pts (22.4%) were grade 4, 20 (29.9%) grade 3, 13 (19.4%) grade 2 and 19 (28.4%) grade 1. Although the ORR to first line (corticosteroid therapy) was 68.6%, 34pts (50.8%) were treated with 2nd line therapies, whom 20pts (30%) with anti-thymocyte globulin (ATG), 9 pts (13.4%) with infliximab and 5pts (7.5%) with ruxolitinib. The response with ruxolitinib was 80%, infliximab 55.6% and ATG 35%. The median OS was 4months [0-69] and was significantly inferior in GI-GVHD grade 3-4 vs grade 1-2 (2 vs 11 months, p=0.018, fig.1). In non-responders, the OS was significantly inferior vs responders (1-year overall survival 3.7 vs 41.2%, P<0.001, fig.2). In univariate analysis, the gender, non-responders patients and grade 3-4 of GI-GVHD were significantly associated with an increased risk of death, but in multivariate analysis only the non-responders patients were independently prognostic factor in OS. Image:Summary/Conclusion: In conclusion, patients with GI-GVHD who did not respond to the first-line therapy and grade 3-4 GI-GVHD had a worse clinical outcome, and the non-responders patients were independently associated with an inferior OS. The first two authors contributed equally to this work.